The effect of endogenous nitric oxide on mechanical ciliostimulation of human nasal mucosa
The effect of endogenous nitric oxide on mechanical ciliostimulation of human nasal mucosa
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DOI：
10.1111/j.1365-2222.2006.02563.x
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发表时间：
2006-10-01
影响因子：
6.1
通讯作者：
Rudack, C.
中科院分区：
文献类型：
--
作者：
Alberty, J.;Stoll, W.;Rudack, C.
背景变应性鼻炎患者鼻呼吸道上皮中诱导型一氧化氮合酶产生的内源性一氧化氮（NO）增加。最近的实验数据表明，内源性NO强烈参与纤毛活动的调节，驱动力的mucociliary transport system.Objective在这项研究中，我们研究了内源性NO对机械刺激的纤毛活动在鼻粘膜外植体model.Methods培养鼻粘膜外植体与TNF-α和细菌脂多糖（LPS），以提高内源性NO的产生。直接在体外NO成像进行了荧光NO指示剂<$A-2 DA和激光扫描共聚焦显微镜。采用光电技术测定纤毛搏动频率（CBF）。在封闭的灌注室中通过两个连续的流量增量进行机械刺激。结果在控制条件下，第一次流量增加时CBF较基础值平均增加30.2%，第二次流量增加时CBF较基础值平均增加30.7%。在TNF-α/LPS刺激的培养物中阻断内源性NO合成使基线CBF降低10.6 +/-2.1%（P < 0.05），但机械纤毛刺激对CBF的影响保持不变（36.0%vs.38.2%hCLUSION总之，内源性NO和Ca 2+依赖的纤毛活动的机械刺激可能使用独立的细胞内信号传导途径。对纤毛活动的两种作用的组合可能改善鼻过敏患者对吸入性过敏原的局部防御。
Background Endogenous nitric oxide (NO) production by the inducible NO-synthase is enhanced in the nasal respiratory epithelium of patients with allergic rhinitis. Recent experimental data suggest endogenous NO to be strongly involved in the regulation of ciliary activity, the driving force of the mucociliary transport system.Objective In this study, we investigated the effect of endogenous NO on mechanical stimulation of ciliary activity in a nasal mucosa explant model.Methods Cultures of nasal mucosa explants were incubated with TNF-alpha and bacterial lipopolysaccharides (LPS) to enhance endogenous NO production. Direct in vitro NO imaging was performed by the fluorescent NO-indicator DAF-2 DA and laser scanning confocal microscopy. Ciliary beat frequency (CBF) was determined using a photoelectric technique. Mechanical stimulation was performed by two consecutive flow increments in a closed perfusion chamber. Endogenous NO-synthesis was blocked by L-NAME before the second flow stimulation.Results Under control conditions the mean rise of CBF relative to baseline was 30.2% during the first flow increment and 30.7% during the second flow increment. Blocking of the endogenous NO synthesis in TNF-alpha/LPS-stimulated cultures reduced baseline CBF by 10.6 +/- 2.1% (P < 0.05) but the effect of mechanical ciliostimulation on CBF remained unchanged (36.0% vs. 38.2%).Conclusions In conclusion, endogenous NO- and Ca2+-dependent mechanical stimulation of ciliary activity probably use independent intracellular signalling pathways. The combination of both effects on ciliary activity is likely to improve the local defence against inhaled allergens in patients with nasal allergies.